{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:34Z","timestamp":1789106854643,"version":"build-2803163510"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-15-00129-P"],"award-info":[{"award-number":["22-15-00129-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Deregulation of alternative splicing has long been associated with aggressive cancer phenotypes characterized by acute or chronic acidosis. Recently, it was hypothesized that this deregulation results from the sequestration of SR-rich splicing factors in nuclear speckles. However, this hypothesis lacked experimental evidence. Here, we demonstrate that, within the pH range consistent with acidosis, phosphorylated SR-rich fragments of splicing factors undergo a phase transition in minimal and multicomponent models of nuclear speckles. This acidification effect resembles the effect of SR dephosphorylation. We explain the molecular basis of this effect and visualize analogous transitions of nuclear speckles in acidified human cells. We also analyze splicing alterations in response to prolonged acidification. The most frequent alteration is exon skipping, consistent with the inaccessibility of SR-rich splicing factors, which normally promote exon inclusion. Our results support the previously proposed hypothesis and deepen the understanding of splicing regulation.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1862962","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:30:17Z","timestamp":1789104617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Acidosis promotes exon skipping through sequestering SR-rich splicing factors in nuclear speckles"],"prefix":"10.3389","volume":"13","author":[{"given":"Alina S.","family":"Shtork","sequence":"first","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel V.","family":"Rubtsov","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia N.","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuliia I.","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina E.","family":"Illarionova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita E.","family":"Bogomiakova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana V.","family":"Sizova","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina M.","family":"Proshkina","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra A.","family":"Strokach","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ksenia M.","family":"Klimina","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria O.","family":"Shender","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey M.","family":"Deyev","sequence":"additional","affiliation":[{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgij P.","family":"Arapidi","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna M.","family":"Varizhuk","sequence":"additional","affiliation":[{"name":"Lopukhin Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency","place":["Moscow, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1038\/s41556-024-01570-0","article-title":"Nuclear speckles regulate functional programs in cancer","volume":"27","author":"Alexander","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/BS.MIE.2020.06.009","article-title":"Methods for characterizing the material properties of biomolecular condensates","volume":"646","author":"Alshareedah","year":"2021","journal-title":"Methods Enzymol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1042\/BCJ20170672","article-title":"Mobilization of a splicing factor through a nuclear kinase\u2013kinase complex","volume":"475","author":"Aubol","year":"2018","journal-title":"Biochem. J."},{"key":"B4","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of alternative pre-messenger RNA splicing","volume":"72","author":"Black","year":"2003","journal-title":"Annu. Rev. Biochem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/pcmr.12811","article-title":"Extracellular acidosis triggers a senescence-like phenotype in human melanoma cells","volume":"33","author":"B\u00f6hme","year":"2020","journal-title":"Pigment. Cell Melanoma Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: a flexible trimmer for illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"B7","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41568-022-00541-7","article-title":"RNA splicing dysregulation and the hallmarks of cancer","volume":"23","author":"Bradley","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"B8","doi-asserted-by":"publisher","first-page":"3568","DOI":"10.1093\/nar\/gkg616","article-title":"ESEfinder: a web resource to identify exonic splicing enhancers","volume":"31","author":"Cartegni","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"10745","DOI":"10.3390\/cimb46100638","article-title":"TRIM25, TRIM28 and TRIM59 and their protein partners in cancer signaling crosstalk: potential novel therapeutic targets for cancer","volume":"46","author":"Chiang","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/s41420-025-02806-0","article-title":"Acidic melanoma microenvironment selects for a senescence-like but also migratory-active subpopulation driving metastatic disease","volume":"11","author":"Chiheb","year":"2025","journal-title":"Cell Death Discov."},{"key":"B11","doi-asserted-by":"publisher","first-page":"194388","DOI":"10.1016\/j.bbagrm.2019.05.006","article-title":"Alternative splicing in lung cancer","volume":"1862","author":"Coomer","year":"2019","journal-title":"Biochimica Biophysica Acta (BBA) - Gene Regul. Mech."},{"key":"B12","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrc.2017.77","article-title":"Tumour acidosis: from the passenger to the driver\u2019s seat","volume":"17","author":"Corbet","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.cmet.2016.07.003","article-title":"Acidosis drives the reprogramming of fatty acid metabolism in cancer cells through changes in mitochondrial and histone acetylation","volume":"24","author":"Corbet","year":"2016","journal-title":"Cell Metab."},{"key":"B14","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1016\/j.tcb.2024.02.002","article-title":"Metabolic regulation of mRNA splicing","volume":"34","author":"Cui","year":"2024","journal-title":"Trends Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"370","DOI":"10.3389\/fphys.2013.00370","article-title":"pH sensing and regulation in cancer","volume":"4","author":"Damaghi","year":"2013","journal-title":"Front. Physiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e0290373","DOI":"10.1371\/journal.pone.0290373","article-title":"Hypothesis-generating analysis of the impact of non-damaging metabolic acidosis on the transcriptome of different cell types: integrated stress response (ISR) modulation as general transcriptomic reaction to non-respiratory acidic stress?","volume":"18","author":"Dubourg","year":"2023","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1261\/rna.037044.112","article-title":"Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms","volume":"19","author":"Erkelenz","year":"2013","journal-title":"RNA"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2404609","DOI":"10.1002\/advs.202404609","article-title":"M 6 a-modified SNRPA controls alternative splicing of ERCC1 exon 8 to induce cisplatin resistance in lung adenocarcinoma","volume":"11","author":"Fan","year":"2024","journal-title":"Adv. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"11329","DOI":"10.1073\/pnas.0604616103","article-title":"Utilization of host SR protein kinases and RNA-splicing machinery during viral replication","volume":"103","author":"Fukuhara","year":"2006","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"10350","DOI":"10.1093\/nar\/gkx759","article-title":"Nuclear speckles: molecular organization, biological function and role in disease","volume":"45","author":"Galganski","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"195","DOI":"10.2217\/nnm.10.162","article-title":"Submicron polymer particles containing fluorescent semiconductor nanocrystals Cdse\/Zns for bioassays","volume":"6","author":"Generalova","year":"2011","journal-title":"Nanomedicine"},{"key":"B23","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s00439-016-1683-5","article-title":"The hnRNP family: insights into their role in health and disease","volume":"135","author":"Geuens","year":"2016","journal-title":"Hum. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1038\/ncomms1998","article-title":"Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion","volume":"3","author":"Girard","year":"2012","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/369678a0","article-title":"A serine kinase regulates intracellular localization of splicing factors in the cell cycle","volume":"369","author":"Gui","year":"1994","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1755-8794-4-35","article-title":"Exon array analysis reveals neuroblastoma tumors have distinct alternative splicing patterns according to stage and MYCN amplification status","volume":"4","author":"Guo","year":"2011","journal-title":"BMC Med. Genomics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1186\/s12885-022-10158-6","article-title":"Inhibition of SRPK1, a key splicing regulator, exhibits antitumor and chemotherapeutic-sensitizing effects on extranodal NK\/T-cell lymphoma cells","volume":"22","author":"He","year":"2022","journal-title":"BMC Cancer"},{"key":"B28","doi-asserted-by":"publisher","first-page":"9666","DOI":"10.1073\/pnas.0403533101","article-title":"A molecular link between SR protein dephosphorylation and mRNA export","volume":"101","author":"Huang","year":"2004","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3524","DOI":"10.12659\/MSM.907798","article-title":"Expression of fibroblast growth factor 5 (FGF5) and its influence on survival of breast cancer patients","volume":"24","author":"Huang","year":"2018","journal-title":"Med. Sci. Monit."},{"key":"B30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s40164-022-00322-w","article-title":"TRIM family contribute to tumorigenesis, cancer development, and drug resistance","volume":"11","author":"Huang","year":"2022","journal-title":"Exp. Hematol. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.celrep.2012.02.001","article-title":"Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins","volume":"1","author":"Huelga","year":"2012","journal-title":"Cell Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"e60579","DOI":"10.7554\/eLife.60579","article-title":"SON and SRRM2 are essential for nuclear speckle formation","volume":"9","author":"Ilik","year":"2020","journal-title":"Elife"},{"key":"B33","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41419-022-05470-9","article-title":"Non-canonical functions of spliceosome components in cancer progression","volume":"14","author":"Ivanova","year":"2023","journal-title":"Cell Death Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"EMBJ2021107640","DOI":"10.15252\/embj.2021107640","article-title":"Exon-independent recruitment of SRSF1 is mediated by U1 snRNP stem-loop 3","volume":"41","author":"Jobbins","year":"2022","journal-title":"EMBO J."},{"key":"B35","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ccell.2018.07.001","article-title":"Comprehensive analysis of alternative splicing across tumors from 8,705 patients","volume":"34","author":"Kahles","year":"2018","journal-title":"Cancer Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e94978","DOI":"10.1371\/journal.pone.0094978","article-title":"Identification of a novel function of CX-4945 as a splicing regulator","volume":"9","author":"Kim","year":"2014","journal-title":"PLoS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.3390\/cancers11071026","article-title":"Spatiotemporal pH heterogeneity as a promoter of cancer progression and therapeutic resistance","volume":"11","author":"Korenchan","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B38","doi-asserted-by":"publisher","first-page":"101306","DOI":"10.1016\/j.jbc.2021.101306","article-title":"Phosphorylation regulates arginine-rich RNA-binding protein solubility and oligomerization","volume":"297","author":"Kundinger","year":"2021","journal-title":"J. Biol. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1006\/bbrc.1997.7913","article-title":"Novel SR-Protein-Specific kinase, SRPK2, disassembles nuclear speckles","volume":"242","author":"Kuroyanagi","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B40","doi-asserted-by":"crossref","DOI":"10.1101\/2025.01.15.633116","volume-title":"Nuclear Speckle Dynamics are Controlled by Polyphosphate Inhibition of CLK Proteins","author":"L\u00e1zaro","year":"2025"},{"key":"B41","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.ccell.2018.07.003","article-title":"Synthetic lethal and convergent biological effects of cancer-associated spliceosomal gene mutations","volume":"34","author":"Lee","year":"2018","journal-title":"Cancer Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1016\/j.apsb.2023.05.022","article-title":"Towards understandings of serine\/arginine-rich splicing factors","volume":"13","author":"Li","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"B43","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s12276-025-01407-2","article-title":"Targeting the splicing factor SNRPB inhibits endometrial cancer progression by retaining the POLD1 intron","volume":"57","author":"Li","year":"2025","journal-title":"Exp. Mol. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","article-title":"Molecular signatures database (MSigDB) 3.0","volume":"27","author":"Liberzon","year":"2011","journal-title":"Bioinformatics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1074\/jbc.RA118.003392","article-title":"Distinct mechanisms govern the phosphorylation of different SR protein splicing factors","volume":"294","author":"Long","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B46","volume-title":"Moderated Estimation of Fold Change and Dispersion for RNA-seq Data with DESeq2","author":"Love","year":"2014"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2728","DOI":"10.1073\/pnas.1320755111","article-title":"Structural basis for nuclear import of splicing factors by human transportin 3","volume":"111","author":"Maertens","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2024","DOI":"10.1016\/j.cell.2026.01.011","article-title":"Nuclear speckles enable processing of RNA from GC-rich isochores","volume":"189","author":"Ma\u0142szycki","year":"2026","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1093\/nar\/gkab063","article-title":"Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation","volume":"49","author":"Martin","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.molcel.2008.03.013","article-title":"The splicing factor SF2\/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1","volume":"30","author":"Michlewski","year":"2008","journal-title":"Mol. Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2201","DOI":"10.1016\/j.molcel.2022.05.018","article-title":"A conceptual framework for understanding phase separation and addressing open questions and challenges","volume":"82","author":"Mittag","year":"2022","journal-title":"Mol. Cell"},{"key":"B52","doi-asserted-by":"publisher","first-page":"6250","DOI":"10.1111\/febs.16057","article-title":"Oncogenic dysregulation of pre-mRNA processing by protein kinases: challenges and therapeutic opportunities","volume":"288","author":"Naro","year":"2021","journal-title":"FEBS J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1016\/j.cellsig.2013.07.022","article-title":"Regulation of inflammation by extracellular acidification and proton-sensing GPCRs","volume":"25","author":"Okajima","year":"2013","journal-title":"Cell. Signal."},{"key":"B54","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.molcel.2013.03.001","article-title":"Genome-wide analysis reveals SR protein cooperation and competition in regulated splicing","volume":"50","author":"Pandit","year":"2013","journal-title":"Mol. Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"B56","doi-asserted-by":"publisher","first-page":"109603","DOI":"10.1016\/j.isci.2024.109603","article-title":"RNA molecules display distinctive organization at nuclear speckles","volume":"27","author":"Paul","year":"2024","journal-title":"iScience"},{"key":"B57","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.cell.2011.08.052","article-title":"A mechanism for the evolution of phosphorylation sites","volume":"147","author":"Pearlman","year":"2011","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1021\/acssensors.2c01813","article-title":"Ratiometric i-Motif-Based sensor for precise long-term monitoring of pH micro alterations in the nucleoplasm and interchromatin granules","volume":"8","author":"Petrunina","year":"2023","journal-title":"ACS Sens."},{"key":"B59","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s10555-019-09792-7","article-title":"Causes, consequences, and therapy of tumors acidosis","volume":"38","author":"Pillai","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"B60","doi-asserted-by":"publisher","first-page":"8262","DOI":"10.1093\/nar\/gkac636","article-title":"Cooperative engagement and subsequent selective displacement of SR proteins define the pre-mRNA 3D structural scaffold for early spliceosome assembly","volume":"50","author":"Saha","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41388-023-02897-y","article-title":"MYCN and SNRPD3 cooperate to maintain a balance of alternative splicing events that drives neuroblastoma progression","volume":"43","author":"Salib","year":"2024","journal-title":"Oncogene"},{"key":"B62","doi-asserted-by":"publisher","first-page":"3515","DOI":"10.1242\/jcs.134411","article-title":"p120-catenin in cancer \u2013 mechanisms, models and opportunities for intervention","volume":"126","author":"Schackmann","year":"2013","journal-title":"J. Cell Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","article-title":"rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-seq data","volume":"111","author":"Shen","year":"2014","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/s41419-026-08478-7","article-title":"Semaphorin 6D drives anti-tumor type I interferon responses to reprogram the tumor microenvironment in colorectal cancer","volume":"17","author":"Shi","year":"2026","journal-title":"Cell Death Dis."},{"key":"B65","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1134\/S1068162025010182","article-title":"Quantitative analysis of biomolecular condensates on a modified support","volume":"51","author":"Shtork","year":"2025","journal-title":"Russ. J. Bioorg. Chem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.cplett.2010.10.063","article-title":"Theoretical pKa prediction of O-phosphoserine in aqueous solution","volume":"501","author":"\u015amiechowski","year":"2010","journal-title":"Chem. Phys. Lett."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.12688\/f1000research.7563.2","article-title":"Differential analyses for RNA-seq: transcript-level estimates improve gene-level inferences","volume":"4","author":"Soneson","year":"2016","journal-title":"F1000Res"},{"key":"B68","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41392-023-01409-4","article-title":"Cdc2-like kinases: structure, biological function and therapeutic targets for diseases","volume":"8","author":"Song","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"B69","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41392-024-01734-2","article-title":"Alternative splicing and related RNA binding proteins in human health and disease","volume":"9","author":"Tao","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"B70","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.molcel.2010.08.011","article-title":"The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation","volume":"39","author":"Tripathi","year":"2010","journal-title":"Mol. Cell"},{"key":"B71","doi-asserted-by":"publisher","first-page":"3694","DOI":"10.1091\/mbc.e12-03-0206","article-title":"SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles","volume":"23","author":"Tripathi","year":"2012","journal-title":"Mol. Biol. Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"112864","DOI":"10.1016\/j.bios.2020.112864","article-title":"Genomic DNA i-motifs as fast sensors responsive to near-physiological pH microchanges","volume":"175","author":"Turaev","year":"2021","journal-title":"Biosens. Bioelectron."},{"key":"B73","doi-asserted-by":"publisher","first-page":"2555","DOI":"10.4161\/cc.5.22.3463","article-title":"Cell cycle synchronization at the G 2\/M phase border by reversible inhibition of CDK1","volume":"5","author":"Vassilev","year":"2006","journal-title":"Cell Cycle"},{"key":"B74","doi-asserted-by":"publisher","first-page":"4369","DOI":"10.3390\/molecules29184369","article-title":"Cross-effects in folding and phase transitions of hnRNP A1 and C9Orf72 RNA G4 in vitro","volume":"29","author":"Vedekhina","year":"2024","journal-title":"Molecules"},{"key":"B75","doi-asserted-by":"publisher","first-page":"2309588","DOI":"10.1002\/advs.202309588","article-title":"CLK2 condensates reorganize nuclear speckles and induce intron retention","volume":"11","author":"Wang","year":"2024","journal-title":"Adv. Sci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41556-022-00903-1","article-title":"Cell cycle-specific phase separation regulated by protein charge blockiness","volume":"24","author":"Yamazaki","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1093\/jmcb\/mjz033","article-title":"Aberrant alternative splicing in breast cancer","volume":"11","author":"Yang","year":"2019","journal-title":"J. Mol. Cell Biol."},{"key":"B78","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1039\/C5MB00663E","article-title":"ReactomePA: an R\/Bioconductor package for reactome pathway analysis and visualization","volume":"12","author":"Yu","year":"2015","journal-title":"Mol. Biosyst."},{"key":"B79","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B80","doi-asserted-by":"publisher","first-page":"113827","DOI":"10.1016\/j.celrep.2024.113827","article-title":"SRRM2 phase separation drives assembly of nuclear speckle subcompartments","volume":"43","author":"Zhang","year":"2024","journal-title":"Cell Rep."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1760","DOI":"10.1016\/j.molcel.2025.03.016","article-title":"Phosphorylation-dependent charge blocks regulate the relaxation of nuclear speckle networks","volume":"85","author":"Zhang","year":"2025","journal-title":"Mol. Cell"},{"key":"B82","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s00412-013-0407-z","article-title":"Regulation of splicing by SR proteins and SR protein-specific kinases","volume":"122","author":"Zhou","year":"2013","journal-title":"Chromosoma"},{"key":"B83","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1021\/pr300630k","article-title":"Toward a comprehensive characterization of a human cancer cell phosphoproteome","volume":"12","author":"Zhou","year":"2013","journal-title":"J. Proteome Res."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1862962\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:30:19Z","timestamp":1789104619000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2026.1862962\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":83,"alternative-id":["10.3389\/fmolb.2026.1862962"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2026.1862962","relation":{},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1862962"}}